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Mario Strazzabosco, MD, PhD

Professor of Medicine
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Additional Titles

Clinical Program Leader, Liver Cancer Program

Co-Director, Yale Liver Center, Internal Medicine

Contact Info

Yale School of Medicine

Department of Medicine (Digestive Diseases), PO Box 208019

New Haven, Connecticut 06520-8019

United States

About

Titles

Professor of Medicine

Clinical Program Leader, Liver Cancer Program; Co-Director, Yale Liver Center, Internal Medicine

Biography

Mario Strazzabosco, MD, PhD, was appointed Director and Clinical Program Leader of the Smilow Liver Cancer Program on January 1, 2017. With expertise in advanced hepatology, Dr. Strazzabosco is an expert in the care of patients with liver cancer. Dr. Strazzabosco returned to Yale after serving as the Founding Chief of the Section of Digestive Diseases, Chair of the Department of Surgery and Translational Medicine, and Vice President of the School of Medicine at the University of Milan. He is internationally known for his work in Hepatology and Liver Transplantation, previously served as Medical Director of Hepatology at Yale, is a recipient of NIH funding, and is a member of several scientific societies in Europe and in the United States. Dr. Strazzabosco holds an appointment as Professor of Medicine (Digestive Diseases) at Yale School of Medicine and as Co-Director of the Yale Liver Center. As leader of the Liver Cancer Program at Smilow Cancer Hospital, Dr. Strazzabosco coordinates the efforts of the team to further develop the program in collaboration with the specialties of Medical Oncology, Interventional Radiology, Surgical Oncology, Hepatology, and Transplantation Surgery.

Appointments

Education & Training

MSc
London School of Economics and Social Sciences, Health Care Economics (2023)
Fellow
University of Padova (1995)
PhD
University of Milan (1993)
Fellow
Yale University School of Medicine (1989)
Resident
University of Padova (1987)
MD
University of Padova (1982)

Research

Overview

The main focus of my laboratory is the pathophysiology and therapy of diseases of the biliary tree (also called cholangiopathies). This is a large group of chronic liver diseases, congenital or acquired, that causes significant morbility and mortality in both the adult and pediatric population. The pathogenesis of biliary tree diseases is still elusive and, contrary to other areas of hepatology, effective treatment is still lacking. Liver transplantation remains the only treatment available for cases progressing to end-stage liver disease. On the other hand, many complications of liver transplantation involve the biliary tree, and biliary cells are intimately involved in liver repair and regeneration. Therefore, the basic scientific interest of the lab nicely complements the clinical interest of the group as it translates into the practice of transplant Hepatology.

Pathophysiology of cholangiopathies.
Previous work from my laboratory has contributed to the understanding of the normal physiology of biliary cells and to the identification of prototypic mechanisms for biliary damage for which a model human cholangiopathy exists (Fig. 1). Among them, the lab is now addressing the pathophysiology and treatment of Cystic Fibrosis cholangiopathy, polycystic liver disease and Alagille syndrome.

Cystic Fibrosis (CF) that alters the ability of the biliary epithelium to secrete Cl - through CFTR, and may leads to sclerosing cholangitis and biliary cirrhosis. We have shown that CFTR loss of function affects bicarbonate transport in biliary duct cells, which in certain circumstances this block can be overcome by purinergic signaling, by aminoglicoside antibiotics and by sulphonylureas. More recent on-going work focuses: a) on the effects of ursodeoxycholic acid (UDCA) on biliary epithelia from CF mice models, and b) the use of cell transplantation strategies to treat genetic diseases of the biliary tree.

Polycystic diseasesof the liver (PLD) are a group of extremely interesting developmental genetic cholangiopathies. In these diseases altered function of ciliary proteins causes dramatic changes in cholangiocyte biology, from altered development resulting in "ductal plate malformations, to altered secretory response to sheer stress, to hyperproliferation, and stimulation of excessive portal fibrogenesis. We have described an increased expression of angiogenic factors in the biliary and cystic epithelium of patients with ADPKD and with Caroli Disease (Fig.2). Angiopoietin-1 and VEGF overexpression may have an autocrine stimulatory effect on cystic cholangiocyte growth. In collaboration with Dr. Somlo and the Yale ADPKD Center and thanks to a novel technique enabling the propagation of primary cholangiocyte cultures from wild-type and PLD transgenic mice, we are planning to explore the intracellular signaling pathways involved in autocrine angiogenic signaling in PLD cystic epithelium and to evaluate the potential inhibitory effect of VEGF signaling blockade on cyst growth in vivo using ADPKD mice.

Alagille Syndrome, a developmental disease of the biliary tree caused by an altered Jaggeded-1/Notch-2 signaling. The patient with Alagille syndrome has severe ductopenia, is jaundiced, and is severely itching, but rarely develops terminal liver diseases and liver fibrosis is negligible. Studies are ongoing to clarify the role of Notch in liver repair and development. In Alagille syndrome there is important cholestasis in the absence of ductular reaction and with an accumulation of intermediate hepatocytes, our hypothesis is that Notch signaling is needed for progenitor cell progression to a biliary phenotype.

Another interest of my group is to understand the role of "activated" biliary cells and liver progenitor cells in liver repair mechanisms. The hypothesis is that, although both mature hepatocytes and biliary cells are able of substantial proliferation, this is restricted to experimental conditions and to rare human conditions, while in most cases of chronic liver diseases, liver repair requires the activation of a population of liver "progenitor cells" closely related to the epithelial cells of the terminal cholangioles. Specific hystochemical markers and a rigorous morphometric approach progenitor cells reaction are used to study with in a number of prototypic diseases.

Finally, the group is interested on hepatocellular carcinoma (HCC) therapy. HCC is one of the most frequent malignant neoplasms worldwide and a leading cause of mortality in the western cirrhotic population. HCC is also an important indication for liver transplantation. Many questions are still open concerning the optimal treatment of HCC. We are studying a prospectively followed up cohort of cirrhotic patients with incident HCC treated according to the BCLC staging system. Studies are planned to implement strategies to reduce recurrence in this population.

Digestive diseases; Cholangiopathies; Pathophysiology of Cholangiopathies

Medical Subject Headings (MeSH)

Cystic Fibrosis; Liver Neoplasms

Research at a Glance

Yale Co-Authors

Frequent collaborators of Mario Strazzabosco's published research.

Publications

2024

Clinical Trials

Current Trials

Clinical Care

Overview

Mario Strazzabosco, MD, PhD, the director and clinical program leader of the Smilow Liver Cancer Program, specializes in the care of patients with liver cancers.

Dr. Strazzabosco enjoys forming lasting relationships with his patients, whom he continues to monitor after they’ve been diagnosed with liver cancer. He and his team are quick to diagnose a recurrence of the disease and treat the chronic liver diseases (like cirrhosis of any cause, fatty liver disease or biliary diseases) that can lead to liver cancer while maintaining as much “liver health” as possible.

“To be diagnosed with liver cancer is the beginning of a journey,” Dr. Strazzabosco says. “And it will be a long one. We'll be together for many, many miles."

Along the way, Dr. Strazzabosco ensures his patients receive coordinated care from the program’s team of experts, including medical oncologists, interventional radiologists, surgical oncologists, hepatologists, and transplantation surgeons. Together, these specialists work to offer a personalized care and to provide oncologic treatments while preserving the function of the liver.

If liver function cannot be preserved, and a liver transplant becomes the best option, Dr. Strazzabosco and his team work closely with the physicians and surgeons of the Yale New Haven Hospital Transplant Center.

What he enjoys most about the job is when patients come back to see him with a happy face. “That’s the best part of my work,” he says, “and that's an example where the program all together works in a coordinated fashion and generates a happy-ending story. It takes a village to provide care to these patients. Each specialist provides his or her part of the care in order to generate a happy face, or what doctors call a 'good outcome.'”

Dr. Strazzabosco is also a professor of medicine (digestive diseases) at Yale School of Medicine and deputy director of the Yale Liver Center. He conducts research on liver regeneration, liver cancer care and a rarer form of the cancer that starts in the bile ducts known as cholangiocarcinoma.

Clinical Specialties

Internal Medicine; Medical Oncology; Hepatology

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Contacts

Academic Office Number
Appointment Number
Mailing Address

Yale School of Medicine

Department of Medicine (Digestive Diseases), PO Box 208019

New Haven, Connecticut 06520-8019

United States

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